Subjects with TC or CC of rs4646903 and AG or GG of rs1048943 genotype have lowest ischemic stroke risk, compared to subjects with TT of rs4646903 and AA of rs1048943 genotype, and OR (95 % CI) was 0.63 (0.42-0.89). rs4646903 minor alleles and interaction between rs4646903 and rs1048943 were associated with decreased IS risk.